To the synthetic organic or polymer chemist, simple methods for forming carbon-carbon bonds are extremely important and valuable tools. “Olefin metathesis,” as is understood in the art, is one such method and refers to the metal-catalyzed redistribution of carbon-carbon bonds. See Trnka and Grubbs (2001) Acc. Chem. Res. 34:18-29. Over the past decade, olefin metathesis has emerged as a powerful carbon-to-carbon bond-forming reaction that is widely used in organic synthesis and polymer science. This is largely due to the development of certain transition metal alkylidene complexes that have proven to be highly active metathesis catalysts. These catalysts, developed by Robert H. Grubbs at the California Institute of Technology, are described, inter alia, in U.S. Pat. Nos. 5,312,940, 5,342,909, 5,831,108, 5,017,071, 5,969,170, 6,111,121, and 6,211,391 to Grubbs et al., and in Bourissou et al. (2000) Chem. Rev. 100:39-91 Trnka and Grubbs (2001), supra. The current “Grubbs catalysts,” in which a central ruthenium atom is substituted with an N-heterocyclic carbene ligand, offer many advantages, including readily tunable steric bulk, vastly increased electron donor character, compatibility with a variety of metal species, improved thermal stability, and tolerance of a wide variety of functional groups on the olefinic reactants. See Scholl et al. (1999) Tetrahedron Lett. 40:2247-2250; Scholl et al. (1999) Org. Lett. 1:953-956; Chatterjee et al. (2000) J. Am. Chem. Soc. 122:3783-3784; and Bielawski et al. (2000) Angew. Chem. Int. Ed. 39:2903-2906.
The ruthenium metathesis catalysts and derivatives thereof have firmly established olefin metathesis as a versatile and reliable synthetic technique for advanced organic synthesis, and have proven to be useful in connection with a number of different types of metathesis reactions, including cross-metathesis (e.g., ethenolysis), ring-closing metathesis (RCM), ring-opening metathesis (ROM), ring-opening metathesis polymerization (ROMP), and acyclic diene metathesis (ADMET) polymerization. The metathesis reaction products have a variety of uses; for example, alpha olefins are useful in the preparation of poly(olefin) polymers, alpha, omega ester-functionalized olefins can be converted to thermoset polymers such as epoxy resins and polyurethanes, and the like. As with any commercially significant chemical processes, however, there is an ongoing interest in improving the purity and yield of the reaction product.
In olefin metathesis, olefin isomerization is one of the side reactions observed that can significantly alter the product distribution and decrease the yield of the desired product, especially with ill-defined catalyst systems. (Ivin, K. J.; Mol, J. C. Olefin Metathesis and Metathesis Polymerization; Academic Press: San Diego, Calif., 1997; p 4.) Additionally, the side products resulting from unwanted isomerization are frequently difficult to separate via standard techniques. Well-defined ruthenium-based olefin metathesis catalysts are generally highly selective for olefin metathesis; however, there have been some reports of olefin isomerization occurring with these catalysts as well. See, e.g., Lehman et al. (2003) Inorg Chim. Acta 345:190-198; Schmidt (2004). Eur. J. Org. Chem, 1865-1880, and references cited therein.) Recently, the Grubbs group has shown that ruthenium hydride species formed from decomposition of catalysts could be responsible for the undesirable isomerization reaction. Hong et al. (2004). J. Am. Chem. Soc. 126:7414-7415. This information has allowed for the development of additives to block the unwanted isomerization reaction by scavenging metal hydrides from decomposed ruthenium catalysts, which, in turn, improves reaction products yields and purities.
Paulson and Pederson, in U.S. Patent Publication No. 2003/0023123 A1, described the use of (1) low temperature reaction conditions, and (2) halogenated alkanes, halogenated aromatics, quinones, halogenated quinones, BHT, and vitamin E as isomerization inhibitors, in order to increase purity in metathesis reactions. There is nevertheless an ongoing need for additional isomerization inhibitors that increase the purity and yield of desired metathesis products.